Immunoradiotherapy for Oropharyngeal Cancer

Recruiting at 1 trial location

Overseen By Joseph A Califano, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Disqualifiers: Solitary lymph nodes < 3 cm

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 11

Duration: 6 weeks

29 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for oropharyngeal cancer?

Research shows that stereotactic body radiotherapy (SBRT) and intensity-modulated radiotherapy (IMRT) are promising treatments for oropharyngeal cancer, with studies indicating positive outcomes in terms of effectiveness and safety. ^{1 2 3 4 5}

How is Stereotactic Radiation different from other treatments for oropharyngeal cancer?

Stereotactic Radiation, also known as Stereotactic Body Radiotherapy (SBRT), is unique because it delivers highly focused radiation doses to the cancer in fewer sessions compared to traditional methods. This makes it a promising option for patients who cannot undergo standard brachytherapy (a type of internal radiation treatment). ^{3 4 5 6 7}

What is the purpose of this trial?

The majority of head and neck cancer patients do not respond to immunotherapies, and clinical responses are often not durable. However, targeting tumors with stereotactic radiation in combination with immunotherapy while sparing draining lymphatics enhances anticancer immunity, resulting in dramatic response in HPV (Human Papilloma Virus) virus related cancers of the throat. This trial will leverage targeted tumor radiation and immunotherapy in advance of standard surgical therapy to improve the response of HPV (Human Papilloma Virus) throat cancer to radiation and immunotherapy.

Research Team

Jospeh A Califano, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for individuals with early-stage HPV-related throat cancer (Stage I T1-2N1M0) that can be surgically removed. Participants must be able to safely undergo pre-surgery radiation and treatment with Evorpacept/Pembrolizumab.

Inclusion Criteria

My condition can be treated with surgery.

My cancer is early-stage HPV-related throat cancer.

I can safely undergo radiation and take Evorpacept/Pembrolizumab.

Exclusion Criteria

I have a single lymph node smaller than 3 cm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Stereotactic radiation therapy (SBRT) delivered to gross tumor volume

1 week

1 visit (in-person)

Treatment

Pembrolizumab and Evorpacept administered every three weeks for 2 cycles

6 weeks

2 visits (in-person)

Surgery

Surgical resection of primary tumor and neck dissection

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life post-treatment

3 years

Multiple visits (in-person and virtual) at 7, 11 weeks, and 3, 12 months

Treatment Details

Interventions

• Evorpacept
• Pembrolizumab
• Stereotactic Radiation

Trial Overview The study tests if targeting throat tumors with precise radiation alongside immunotherapy drugs, Evorpacept and Pembrolizumab, before surgery can improve the body's response to the cancer in those affected by HPV.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Stereotactic radiation therapy (SBRT (8GyX3)) will be delivered to gross tumor volume (GTV) +3mm, followed by Pembrolizumab 200 mg IV and Evorpacept 45 mg/kg IV every three weeks x 2 cycles followed by surgical resection of primary tumor and neck dissection.

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Findings from Research

A multi-institutional study involving 69 patients with early oropharyngeal cancer showed that intensity-modulated radiation therapy (IMRT) achieved a low 2-year local-regional failure rate of 9%, indicating high tumor control rates without the use of chemotherapy.

While the treatment resulted in significant late toxicities, particularly xerostomia (dry mouth), the severity of these side effects decreased over time, with 55% of patients experiencing Grade 2 or higher xerostomia at 6 months, dropping to 16% by 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Eisbruch, A., Harris, J., Garden, AS., et al.[2022]

In a study comparing 26 patients receiving radiotherapy with cetuximab (cet-RT) to 27 patients receiving chemotherapy (chemo-RT) for HPV+ oropharyngeal cancer, both groups showed similar functional outcomes and quality of life over time, despite some initial worsening in swallowing and quality of life scores.

The results suggest that using cetuximab instead of chemotherapy for treatment de-intensification in HPV+ oropharyngeal cancer may not provide significant advantages, as both treatment approaches yielded excellent clinical outcomes without notable differences in patient functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons of dysphagia and quality of life (QOL) in comparable patients with HPV-positive oropharyngeal cancer receiving chemo-irradiation or cetuximab-irradiation. Samuels, SE., Tao, Y., Lyden, T., et al.[2018]

Frameless stereotactic body radiotherapy (SBRT) was found to be a safe and effective treatment option for boosting primary oropharyngeal cancers in 51 patients who were not suitable for standard brachytherapy, achieving 2-year local control, disease-free survival, and overall survival rates of 86%, 80%, and 82%, respectively.

The treatment was well tolerated with no severe (Grade 4 or 5) toxicities reported, and only 28% of patients experienced Grade 2 or higher late toxicity, indicating that SBRT can be a viable alternative with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy: a promising treatment option for the boost of oropharyngeal cancers not suitable for brachytherapy: a single-institutional experience. Al-Mamgani, A., Tans, L., Teguh, DN., et al.[2012]

Intensity-modulated radiotherapy (IMRT) using helical tomotherapy for oropharyngeal carcinoma showed promising clinical outcomes, with a 3-year overall survival rate of 80% and a progression-free survival rate of 68% among 93 patients followed for a median of 40 months.

The treatment effectively preserved parotid gland function, with only 23% of patients experiencing Grade 2 xerostomia (dry mouth) after 2 years, indicating a favorable safety profile alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety. Kimura, K., Kodaira, T., Tomita, N., et al.[2018]

Intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma showed promising 5-year local control rates, with 87% overall and varying by cancer stage, indicating its efficacy in managing advanced disease.

The treatment resulted in a 5-year cause-specific survival rate of 85% and an overall survival rate of 76%, with a relatively low incidence of severe late complications (8%), suggesting that IMRT is a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. Mendenhall, WM., Amdur, RJ., Morris, CG., et al.[2022]

Intensity modulated radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

The two-step intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer resulted in favorable 5-year overall survival rates of 80% for stage I and 64% for stage IVA-B, indicating effective treatment across various stages of the disease.

Patients with HPV/p16-positive oropharyngeal cancer had significantly better overall survival compared to those who were HPV/p16-negative, highlighting the importance of HPV status in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial Clinical Experience and Validation of Clinical Staging. Tatebe, H., Doi, H., Ishikawa, K., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Comparisons of dysphagia and quality of life (QOL) in comparable patients with HPV-positive oropharyngeal cancer receiving chemo-irradiation or cetuximab-irradiation. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy: a promising treatment option for the boost of oropharyngeal cancers not suitable for brachytherapy: a single-institutional experience. [2012]

4. England pubmed.ncbi.nlm.nih.gov

Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. [2006]

7. Greece pubmed.ncbi.nlm.nih.gov

Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial Clinical Experience and Validation of Clinical Staging. [2019]